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SYNAPTIC TRANSMISSION

SYNAPTIC TRANSMISSION

1897: Charles Sherrington- “synapse”

The process of information transfer at a synapse

Plays role in all the operations of the nervous system

Information flows in one direction: Neuron to target cell

First neuron = Presynaptic neuron

Target cell = Postsynaptic neuron

Types of synapses:

1) Chemical (1921- Otto Loewi)

2) Electrical (1959- Furshpan and

Potter)

ELECTRICAL SYNAPSES

Gap junction

Cells are said to be “electrically coupled”

Flow of ions from cytoplasm to cytoplasm

and in both directions

Transmission is fast

ELECTRICAL SYNAPSES

An AP in the pre synaptic cell, generate a PSP (post synaptic potential) in the

post synaptic cell

If several PSPs occur simultaneously to excite a neuron this generates an AP

(Synaptic integration)

CHEMICAL SYNAPSES

Key elements:

Synaptic cleft (wider the gap junction);

Presynaptic element (usually an axon terminal )

Synaptic vesicles (storage of neurotransmitter)

Secretory granules (bigger vesicles)

Postsynaptic density (receptor that converts chemical signal

into electrical signal )

Postsynaptic cell

CNS SYNAPSES

Axodendritic: Axon to dendrite

Axosomatic: Axon to cell body

Axoaxonic: Axon to axon

Dendrodendritic: Dendrite to dendrite

Gray’s Type I: Asymmetrical,

excitatory

Gray’s Type II: Symmetrical,

inhibitory

NEUROMUSCULAR JUNCTION

Synaptic junction outside the CNS Studies of NMJ established principles of synaptic transmission One of the largest and faster synapses in the body

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

Basic Steps

• Neurotransmitter synthesis

• Load neurotransmitter into synaptic vesicles

• Vesicles fuse to presynaptic terminal

• Neurotransmitter spills into synaptic cleft

• Binds to postsynaptic receptors

• Biochemical/Electrical response elicited in postsynaptic cell

• Removal of neurotransmitter from synaptic cleft


TRANSMISSION

Neurotransmitters

Amino acids: Small organic molecules

stored in and released from synaptic

vesicles (Glutamate, Glycine, GABA)

Amines: Small organic molecules stored

in and released from synaptic vesicles

(Dopamine, Acetylcholine, Histamine)

Peptides: Short amino acid chains (i.e.

proteins) stored in and released from

secretory granules (Dynorphin,

Enkephalins)


TRANSMISSION

Neurotransmitter Synthesis and Storage A part from amino acids, amines and peptides are synthesized from precursors only in neuron

that release them.

Amine and amino acids are synthesized in the axon terminal and the take up by the vesicles

with the help of the transportes .

Peptides are synthesized in the rough ER, eventually split in the Golgi apparatus and then

carried to the axon terminal in the secretory granules


TRANSMISSION

Neurotransmitter release by exocytosis AP opens voltage gate calcium channel

Process of exocytosis stimulated by release of intracellular calcium, [Ca2+]I, due to the AP.

Vesicle membrane fuses into presynaptic membrane with subsequent release of neurotransmitter

Vesicle membrane recovered by endocytosis and then refilled with new neurotransmitter


TRANSMISSION

Neurotransmitter Receptors and Effectors (postsynaptic cell)

Ionotropic: Transmitter-gated ion channels Metabotropic: G-protein-coupled receptor

Autoreceptors: Presynaptic receptors sensitive to neurotransmitter released by presynaptic

terminal. Act as safety valve to reduce release when levels are high in synaptic cleft

(autoregulation)


TRANSMISSION

IPSP: Transient hyperpolarization

of postsynaptic membrane

potential caused by presynaptic

release of neurotransmitter

EPSP: Transient postsynaptic

membrane depolarization by

presynaptic release of

neurotransmitter


TRANSMISSION

Neurotransmitter Recovery and Degradation Neurotransmitter must be cleared from the synaptic cleft. Different ways.

Diffusion: Away from the synapse

Reuptake: Neurotransmitter re-enters presynaptic axon terminal

Enzymatic destruction inside terminal cytosol or synaptic cleft

Desensitization: e.g., AChE cleaves Ach to inactive state

PRINCIPLES OF SYNAPTIC INTEGRATION

Synaptic Integration

Process by which multiple synaptic potentials combine within one postsynaptic

neuron


Quantal Analysis of EPSPs The synaptic vesicle is the elementary units of synaptic transmission The amplitude of an EPSP is some multiple of the response to the content of a vesicle (quantum) Quantal analysis is used to determine number of vesicles that release during neurotransmission Miniature postsynaptic potential (“mini”) are normally generated spontaneously


EPSP Summation Allows for neurons to perform sophisticated computations. EPSPs are added together to

produce significant postsynaptic depolarization. Two types:

Spatial: EPSP generated simultaneously in different spaces

Temporal: EPSP generated at same synapse in rapid succession


Inhibition Action of synapses to take membrane potential away from action potential threshold

IPSPs and Shunting Inhibition Excitatory vs. inhibitory synapses: Bind

different neurotransmitters (GABA or Glycine),

allow different ions to pass through channels

(Chloride, Cl-)

Membrane potential less negative than -65mV

= hyperpolarizing IPSP

Shunting Inhibition: Inhibiting current flow from

soma to axon hillock


The Geometry of Excitatory and Inhibitory Synapses

Excitatory synapses (Glutamate) usually have Gray’s type I morphology

Clustered on soma and near axon hillock

Inhibitory synapses (GABA, Glycine) have Gray’s type II morphology

Gray’s Type I: Asymmetrical, excitatory

Gray’s Type II: Symmetrical, inhibitory


Modulation

Synaptic transmission that modifies effectiveness of EPSPs generated by other

synapses with transmitter-gated ion channels

Example: Activating NE β receptor

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